Biochemistry, Biophysics, and Structural Biology Commons^™

Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei

Markey Cancer Center Faculty Publications

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …

Methylene Blue Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Oocytes, Dmytro Isaev, Keun-Hang Susan Yang, Georg Petroianu, Dietrich Ernst Lorke, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The effects of methylene blue (MB) on cromakalim-induced K⁺ currents were investigated in follicle-enclosed Xenopus oocytes. In concentrations ranging from 3–300 μM, MB inhibited K⁺ currents (IC₅₀: 22.4 μM) activated by cromakalim, which activates K_ATP channels. MB inhibited cromakalim-activated K⁺ currents in a noncompetitive and voltage-independent manner. The respective EC₅₀ and slope values for cromakalim-activation of K⁺ currents were 194 ± 21 µM and 0.91 for controls, and 206 ± 24 µM and 0.87 in the presence of 30 μM MB. The inhibition of cromakalim-induced K⁺ currents by MB was not …

Quantification Of Nuclear Dynamics During Epithelial Remodeling, Noah De Leeuw

Electronic Theses and Dissertations

The morphogenesis of developing tissues is contingent on an extensive array of rearrangements in cellular shape, position and identity at large and small scales. One commonly used process to reshape tissues is the cell intercalation-driven elongation of a tissue in a common axis, in which rows of epithelial cells undergo oriented intercalation in a directional fashion. In most models of intercalation, cells are treated as homogeneous objects directed in their shape changes by cortical forces localized along cell-cell interfaces or tricellular junctions. However, less attention has been paid to how inhomogeneities in mechanical resistance of their own internal structures affects …

Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar

Theses and Dissertations

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Major part of DDR is coordinated by DNA damage checkpoint (DDC). In addition to DDC, eukaryotic cells also have DNA replication checkpoint (DRC) that is distinct from the DDC and specifically signals slowly progressing or arrested replication forks. DDR involves stalling or arrest of the cell cycle, initiation of DNA repair, and altered regulation of transcription, translation, and the ubiquitin-proteasome system. DDR also triggers transcription shut-off of histone genes. One of the key outcomes of DDC/DRC activation is the increased synthesis of the deoxyribonucleoside triphosphates (dNTPs), …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

Developing Red Fluorescent Zn2+ Sensors And Characterizing Zn2+ Homeostasis In Mucolipidosis Type Iv Disease, Anna M. Dischler

Electronic Theses and Dissertations

Zinc (Zn²⁺) is a divalent, redox-inert metal that plays a vital role in many cellular processes either by acting as a catalytic cofactor or a labile signaling molecule in the cytoplasm. Cytosolic Zn²⁺ levels are tightly regulated to stay within a narrow window of concentrations, but fluctuations in Zn²⁺ signals have been detected in a variety of cells. We developed a genetically encoded, single red fluorescent protein (RFP) based Zn²⁺ sensor, RZnP1, that can be used alongside green-wavelength sensors for the simultaneous detection of different signaling molecules within the same cells or among different subcellular …

Identifying The Role Of Phospholipase D1 And Phosphatidic Acid In Exocytosis, Broderick L. Bills

Electronic Theses and Dissertations

Exocytosis is an essential process for intercellular communication in eukaryotic cells. This process involves significant changes in membrane curvature, and lipids and curvature-sensing proteins can assist these processes. One protein in particular, phospholipase D1 (PLD1), and its product, the lipid phosphatidic acid (PA), are involved in multiple exocytic processes. However, PLD1 and PA’s role in this process has remained unclear. In this work, PLD1 and the production of PA were visualized during exocytosis, and PA localization to regions of membrane curvature was established. Together, these results support the hypothesis that PLD1 production of PA stabilizes negative curvature during membrane fusion. …

Dcaf14 Regulates Cdt2 To Promote Set8-Dependent Replication Fork Protection, Neysha Tirado-Class, Caitlin Hathaway, Anthony Nelligan, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4–RING E3 ubiquitin ligase (CRL4) complexes. CDT2 is responsible for PCNA-coupled proteolysis of substrates CDT1, p21, and SET8 during S-phase of cell cycle. DCAF14 functions at stalled replication forks to promote genome stability, but the mechanism is unknown. We find that DCAF14 mediates replication fork protection by regulating CRL4CDT2 activity. Absence of DCAF14 causes increased proteasomal degradation of CDT2 substrates. When forks are challenged with replication stress, increased CDT2 function causes stalled fork collapse and impairs fork recovery in DCAF14-deficient conditions. We further show that stalled fork protection …

Otud5 Limits Replication Fork Instability By Organizing Chromatin Remodelers, Angelo De Vivo, Hongseon Song, Yujin Lee, Neysha Tirado-Class, Anthony Sanchez, Sandy D. Westerheide, Huzefa Dungrawala, Younghoon Kee

Molecular Biosciences Faculty Publications

Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts is crucial in preserving the integrity of replication forks. Various chromatin remodelers, such as histone chaperone and histone deacetylases are known to modulate replication stress, but how these factors are organized or collaborate are not well understood. Here we found a new role of the OTUD5 deubiquitinase in limiting replication stress. We found that OTUD5 is recruited to replication forks, and its depletion causes replication fork stress. Through its C-terminal disordered tail, OTUD5 assembles a complex containing FACT, HDAC1 and HDAC2 at replication forks. A …

The Identification Of Two M20b Family Peptidases Required For Full Virulence In Staphylococcus Aureus, Nathanial James Torres, Devon Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey Neil Shaw

Molecular Biosciences Faculty Publications

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival …

S-Acylation Is A Key Regulator Of Orai1/Stim1-Mediated Store-Operated Calcium Entry In T Cells, Savannah J. West Diaz

Dissertations and Theses (Open Access)

Orai1 and STIM1 proteins are the essential components of the Ca²⁺ release activated Ca²⁺ (CRAC) channel which is required for store-operated Ca²⁺ entry (SOCE) in T cells and subsequent signaling events leading to T cell activation, proliferation, and differentiation. Plasma membrane (PM)-localized Orai1 is the pore-forming subunit of the CRAC channel, and STIM1 is the Ca²⁺ sensor localized to the endoplasmic reticulum (ER) membrane in quiescent T cells. T cell receptor (TCR) stimulation leads to depletion of ER Ca²⁺ stores resulting in Ca²⁺ no longer being bound to STIM1. This activates STIM1 by triggering …

Testing Ssa4:Ade3 Reporters For Mcs Screening, Karah Edmonds, Rebecca Adams

Science University Research Symposium (SURS)

In eukaryotic cells, after transcription, mRNA is escorted from the nucleus to the cytoplasm to be translated. This process, called mRNA export, is essential for gene expression. However, when the cell exists in stressful conditions, mRNA export becomes regulated, and only select transcripts, including the stress-responsive SSA4 mRNA, can be exported. This project aims to uncover the mechanism of selective SSA4 mRNA export by generating a reporter that enables phenotypically visible expression under stressful conditions. Specifically, the ADE3 ORF was placed under the regulatory sequence of SSA4, which was anticipated to induce a red color for colonies only following stress. …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

Characterization Of Parp1-Dependent Poly-Adp-Ribosylation Of Sprtn, Quincee Simonson

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) are a type of DNA lesion that form when proteins become covalently linked to DNA. It is estimated that replicating cells experience approximately 6,000 DPCs per day per genome during exponential growth (Ruggiano & Ramadan, 2021). If left unrepaired, DPCs can be lethal to cells. For this reason, cells have evolved multiple pathways to repair or bypass DPCs to survive. One such pathway involves SPRTN, a nuclear metalloprotease that plays a key role in the repair of DPCs through direct proteolysis (Lopez-Mosqueda et al., 2016; Vaz et al., 2016). Once SPRTN degrades the bulky protein component of …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Dual Mechanisms Contributing To Pyruvate Dehydrogenase Activity Deficiency In A Barth Syndrome Cell Model, Zhuqing Liang

Wayne State University Dissertations

Barth syndrome (BTHS) is a rare genetic disease that results from mutations in the TAFAZZIN gene, which encodes the cardiolipin (CL) remodeling enzyme tafazzin (Taz). The mechanisms linking perturbation of CL remodeling and the pathological features of BTHS are not understood. We have recently reported that intermediary metabolism is perturbed in BTHS, and activity of the metabolic gatekeeper enzyme pyruvate dehydrogenase (PDH) is deficient in BTHS models. The mechanism whereby PDH is regulated by Taz is unknown, and this knowledge gap represents an obstacle to the development of therapeutics to treat BTHS. Using an established C2C12 myoblast model of BTHS, …

Metabolic Reprogramming Driven By Ezh2 Inhibition Depends On Cell–Matrix Interactions, Teresa W-M Fan, Jahid M. M. Islam, Richard M. Higashi, Penghui Lin, Christine F. Brainson, Andrew N. Lane

Markey Cancer Center Faculty Publications

EZH2 (Enhancer of Zeste Homolog 2), a subunit of Poly- comb Repressive Complex 2 (PRC2), catalyzes the trimethyla- tion of histone H3 at lysine 27 (H3K27me3), which represses expression of genes. It also has PRC2-independent functions, including transcriptional coactivation of oncogenes, and is frequently overexpressed in lung cancers. Clinically, EZH2 in- hibition can be achieved with the FDA-approved drug EPZ- 6438 (tazemetostat). To realize the full potential of EZH2 blockade, it is critical to understand how cell-cell/cell-matrix interactions present in 3D tissue and cell culture systems in- fluences this blockade in terms of growth-related metabolic functions. Here, we show that …

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …

Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden

Markey Cancer Center Faculty Publications

Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.

Methods To identify the potential markers of SkM‑derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, …

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …

Identification Of A Dna Polymerase Alpha Gene Sequence In Thermomyces Lanuginosus Fungus, Nathan Williams

Honors Program Theses

With cell growth being the main focus of our research, we chose to study DNA polymerase alpha. DNA polymerase alpha is likely to be involved in cell growth as it is the enzyme that starts DNA replication. Control of this enzyme might lead to decreased cell growth in cancer or increased cell growth in damaged spinal cord tissue. We chose the thermophilic fungus Thermomyces lanuginosus for the study of the enzyme due to the ability to compare the enzyme’s activity during fungal growth at different temperatures. Thermomyces exhibits rapid growth at high temperatures and slow growth at low temperatures. Studying …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Investigating Changes In Er-To-Golgi Protein Transport Following A Short Calcium Pulse: Roles Of Alg-2 And Peflin, Alaa Mohammed Yosri Shaheen

Graduate Student Theses, Dissertations, & Professional Papers

The ER-Golgi interface is a very dynamic environment that involves the movement of protein-loaded vesicles forward and backward. The movement of COPII-coated vesicles from the ER to the Golgi is the initial step in the movement of secreted, organellar, and cell surface proteins toward their final destinations. Many factors can regulate this step, including cytosolic calcium increases. In this study, we examined the effect of a transient calcium pulse on recruitment to ER exit sites of cargo proteins for ER export, the calcium-sensitive regulatory proteins apoptosis-linked gene 2 (ALG-2) and peflin, and the COPII outer coat subunits Sec31A and Sec13. …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik

Theses & Dissertations

Human AP Endonuclease 1 (APE1) is the primary enzyme in the base excision repair (BER) pathway that repairs apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome. Recently, through genome-wide mapping analysis, we have shown that APE1, as well as its post-translationally modified form, acetylated APE1 (AcAPE1), is enriched in the gene regulatory regions. The APE1/AcAPE1-enriched regions also harbor Guanine (G)-rich sequences that fold into DNA secondary structures called G-quadruplexes (G4s). Our lab has demonstrated a strong genome-wide correlation between the occurrence of G4 structures and the binding of APE1 and AcAPE1. However, it is unknown whether …